Multiple sclerosis is a devastating, autoimmune neurodegenerative disease, involving myelin sheath degradation and inflammation of the brain and spinal cord. MS patients have neural cell membrane defects in these areas involving calcium ion up regulation of calpain and subsequent degradation of nerve tissue. Although MS therapies do exist today, they are considered only partially satisfactory due to lack of universal effectiveness and accompanying side effects. The Company's product candidate, NEURODUR, has been shown effective in animal models. NEURODUR combines the nerve cell targeting transport molecule, taurine, with the calpain inhibitor, leupeptin. NEURODUR data from MS mouse models are promising as they demonstrated a direct delivery to and positive impact on the brain and spinal cord. In an MS mouse model, brain inflammation was evident in the non-treated mice, but not in the NEURODUR treated mice. All of the NEURODUR treated mice lived while all of the  non-treated mice died. Disease Background Multiple sclerosis has an unknown etiology but is thought to be an autoimmune disease that affects the central nervous system (CNS). The CNS consists of the brain, spinal cord, and the optic nerves. Surrounding and protecting the nerve fibers of the CNS is a fatty tissue called myelin, which helps nerve fibers conduct electrical impulses. In MS, myelin is lost in multiple areas, leaving scar tissue called sclerosis. When myelin or the nerve fiber is destroyed or damaged, the ability of the nerves to conduct electrical impulses to and from the brain is disrupted, and this produces various symptoms of the disease. There are four different clinical courses of MS, each of which might be mild, moderate, or severe. Research and Development In multiple sclerosis (MS), the main pathology consists of the degradation of myelin proteins which results in the destabilization of the myelin sheath. Calpain, a calcium-activated protease has been implicated in myelinolysis. Calpain is significantly elevated in the white matter of MS patients and is increasingly expressed in activated microglia and macrophages in MS patients, suggesting its role in the pathophysiology of this disease. Some studies have demonstrated the role of calpain inhibition with the tripeptide protease inhibitor, leupeptin, in peripheral nerve, and its effect in suppressing EAE (experimental autoimmune encephalomyelitis, the only animal model for MS), in rats. The main limitation of this protease inhibitor was its ability to cross the blood brain barrier to reach the site of action. To overcome this obstacle, Drs. Stracher and Kesner, scientists at Ceptor Corporation, synthesized a compound utilizing the taurine transport system to overcome the blood brain barrier and enter into the CNS. In preliminary studies, induction of EAE and treatment with NEURODUR was undertaken. Thirty six, seven-week old female C57BL/6J mice were used. The average clinical scores (ACS) for all mice in a particular treatment group or control group were evaluated daily for clinical signs of disease for up to 19 days after inoculation. Clinical severity was assessed on a scale of 0-6, 0 meaning no abnormality and 6 meaning moribund or death. The ACS for B6 mice induced with EAE was substantially reduced with the NEURODUR treatment. The data found between the untreated and NEURODUR treated animals were statistically significant. The ultimate goal is to develop a therapeutic compound that can protect myelin and nerve fibers from damage caused by calpain activity of microglia and macrophages in MS. Further development will require toxicology and clinical studies. Demographics Approximately 1 in 700 to 1 in 1000 people develops MS with this incidence being about two to three fold more common in women than men. It is known that 400,000 people have been diagnosed with MS in the U.S. while the worldwide prevalence is estimated at about 2.5 million. There are currently several forms of beta-serons on the market at an average cost of $10,000-$14,000 per year per patient. Research continues in this area as the beta-serons are not considered a panacea. MS is not an orphan indication and is a market fairly well developed due to multiple competitors. In staying with its business model, the Company plans to out-license NEURODUR for MS. Partnering efforts are on-going and will continue, but if the budget allows, the Company will develop NEURODUR through the IND stage making it more attractive and valuable as an out-licensing opportunity. |